Citations 1
Murine modeling of IDH-mutant 1p/19q-codeleted oligodendroglioma reveals genotype specific phenotypes
Kundu, Ipsita, Toro, Nicolas, Langhnoja, Jaldeep, Ayyagari, Rithvik V, Cronk, James C, Arounleut, Phonepasong, Esqueda, Luis Tron, Fuller, Christine , Viswanath, Pavithra, Heimberger, Amy B. , Horbinski, Craig M, Phoenix, Timothy N. , Phoenix, Timothy N , Toro, Nicolas, Mochizuki, Aaron Y. , Langhnoja, Jaldeep , Cronk, James, Reel, Sarah Martin , Esqueda, Luis Tron , Viswanath, Pavithra , Heimberger, Amy B. , Horbinski, Craig
No container title available | May 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Oligodendroglioma is a primary central nervous system tumor classified by the presence of isocitrate dehydrogenase (IDH) mutations and codeletion of 1p/19q. Here we describe the generation of an IDH-mutant 1p/19q-codeleted oligodendroglioma mouse model using in utero electroporation. We identified IDH1 R132H , PIK3CA E545K , Cic KO , Fubp1 KO and Cdkn2a KO as the optimal combination (termed Oligo Cdkn2a ) to drive fully penetrant tumors that histologically resemble human grade II/III IDH-mutant, 1p/19q-codeleted oligodendroglioma. Replacing Cdkn2a with Trp53 loss in this mouse model shifted tumor histology towards high grade astrocytoma. Oligo Cdkn2a tumors displayed metabolic and transcriptional changes associated with IDH and CIC mutations, and single cell sequencing identified a bias towards oligodendrocyte differentiation compared to an IDH wild-type glioblastoma mouse model. Oligo Cdkn2a tumors represent the first mouse model system to recapitulate the genetic, histological and transcriptional features of human IDH-mutant 1p/19q-codeleted oligodendrogliomas, offering a platform to further dissect tumor biology and test new therapeutic strategies.